Factors contributing to pre-treatment loss to follow-up in adults with pulmonary tuberculosis: a qualitative evidence synthesis of patient and healthcare worker perspectives

ABSTRACT Background Since 2018, over 14 million people have been treated for tuberculosis (TB) globally. However, pre-treatment loss to follow-up (PTLFU) has been shown to contribute substantially to patient losses in the TB care cascade with subsequent high community transmission and mortality rates. Objective To identify, appraise, and synthesise evidence on the perspectives of patients and healthcare workers on factors contributing to PTLFU in adults with pulmonary TB. Methods We registered the title with PROSPERO (CRD42021253212). We searched nine relevant databases up to 24 May 2021 for qualitative studies. Two review authors independently reviewed records for eligibility and extracted data. We assessed methodological quality with the Evidence for Policy and Practice Information Centre tool and synthesised data using the Supporting the Use of Research Evidence framework. We assessed confidence in our findings using Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERQual). Results We reviewed a total of 1239 records and included five studies, all from low- and middle-income countries. Key themes reported by patients and healthcare workers were communication challenges among healthcare workers and between healthcare workers and patients; knowledge, attitudes, and behaviours about TB and its management; accessibility and availability of facilities for TB care; and human resource and financial constraints, weakness in management and leadership in TB programmes. Patients’ change of residence, long waiting times, and poor referral systems were additional factors that contributed to patients disengaging from care. We had moderate confidence in most of our findings. Conclusion Findings from our qualitative evidence synthesis highlight multiple factors that contribute to PTLFU. Central to addressing these factors will be the need to strengthen health systems and offer people-centred care.


KEYWORDS
Tuberculosis; pre-treatment loss to follow-up; qualitative evidence synthesis; healthcare system; TB care cascade; people-centred care Background Tuberculosis (TB) remains a major cause of morbidity and mortality in many low-and middle-income countries (LMICs) [1]. Despite numerous efforts, resources, and research directed towards TB, these endeavours have not translated to sufficient improvement in health outcomes. According to the World Health Organization (WHO), TB incidence has been decreasing globally at a rate of 2% per year; however, the reduction was not fast enough to reach the 2020 milestone of the WHO End TB Strategy [2,3]. The global targets included a reduction in TB incidence and mortality of 20% and 35%, respectively, from 2015 to 2020. However, in 2020, these indicators fell short at 11% and 9% respectively, with the incidence being around 50% and mortality around 25% of the way to the 2020 milestone. Africa has been making good progress with reductions of 19% (incidence) and 18% (mortality), though these percentages are still below the 2020 milestone [3]. Sustaining these improvements will be challenging because owing to the COVID-19 pandemic, globally, deaths from TB are increasing for the first time in a decade [3].
Delays in diagnosis and initiation of effective treatment contribute to challenges in TB care [3,4]. Therefore, access to rapid diagnostics and treatment will play a key role in reducing morbidity and mortality. The TB care cascade described by Subbaraman, and colleagues demonstrated that many patients are lost to follow-up after being diagnosed with TB, but before starting treatment [5]. These patients continue to spread TB in the community and most die because of the disease [6]. In a systematic review that included 23 studies, MacPherson and colleagues found that the overall percentage of pre-treatment loss to follow-up (PTLFU) ranged from 4% to 38%, with studies from Africa ranging from 6% to 38% [6].
Given that many people diagnosed with TB experience PTLFU, it is important to understand the factors that contribute to this attrition to come up with effective interventions. Several studies have highlighted reasons that lead patients to drop out before starting treatment without looking at the challenges experienced during the linkage to care [5][6][7]. Quantitative research suggests that patients face healthcare system barriers that may interfere with their receiving care leading to PTLFU [6][7][8].
There are limited qualitative data to provide more insight into PTLFU. Therefore, conducting this qualitative evidence synthesis (QES), where we systematically searched for qualitative primary studies and summarised their findings, will assist in generating comprehensive evidence on contributors to PTLFU that goes beyond the findings of a single study. The QES will give an understanding of how different factors and contexts influence PTLFU through the perceptions of patients and healthcare workers (HCWs). This in turn will guide us in coming up with effective approaches to reduce PTLFU. To our knowledge, no other QES on perspectives and experiences of patients and HCWs on contributing factors to PTLFU has been conducted so far.
The objective of this QES was to identify, appraise, and synthesise evidence on the perspectives and experiences of patients and HCWs on factors contributing to PTLFU in adults with pulmonary TB.

Methods
We registered the title with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42021253212 and we published the protocol in the open science framework [9]. We have reported this QES according to the Enhancing transparency in reporting the synthesis of qualitative research ENTREQ statement [10].

Criteria for considering studies for the QES
We included primary studies that used qualitative study methodology to describe the experiences and perspectives of patients (adults aged ≥18 years with pulmonary TB) and HCWs on PTLFU and studies that focused on PTLFU. We defined PTLFU as people in a national TB care programme who received a diagnosis of TB based on at least one positive smear, culture, or molecular WHO-recommended rapid diagnostic test (mWRD) but did not start TB treatment including those who died before starting treatment [6,8,11]. We included studies that used both qualitative methods for data collection (e.g. focus group discussions, individual interviews, observation, brainstorming, open-ended survey questions) and qualitative methods for data analysis (e.g. thematic analysis, framework analysis, grounded theory). For studies that used mixed methods, we included only data that had been collected and analysed using qualitative methods. We included studies from all geographical settings. We excluded studies that collected data using qualitative methods but did not analyse the data using qualitative analysis methods (e.g. open-ended survey questions where the response data were analysed using descriptive statistics only).

Identification of studies
We conducted a comprehensive literature search in the following databases: MEDLINE (Ovid from 1946), Cochrane Library (Issue 5 of 12 May 2021), EMBASE (Ovid from 1947), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Global Index Medicus, LILACS, HERDIN, Science Citation Index and Social Science Citation Index. We performed the search up to 24 May 2021 without date restriction. We only searched for studies written in English since we did not have resources to support the translation of non-English language studies. A detailed description of the identification of studies and full search strategy can be found in Supplemental material 1. We entered the search output into EndNote to delete duplicates. Thereafter, we used Covidence, an online platform for systematic reviews for screening and study selection [12].

Selection of studies
MM with either BN or EJO independently screened titles and abstracts for relevance. Thereafter, we obtained full texts for the selected titles and abstracts. MM with either BN or EJO independently assessed full texts against eligibility criteria using Covidence to come up with the final list of the included studies [12]. We documented the reasons for excluding the studies. We resolved any disagreements that arose at each stage through discussion and where necessary by consultation with a third review author (KRS).

Data collection and management
We extracted data using a structured format, the Supporting the Use of Research Evidence (SURE) framework, to retrieve information [13]. To ensure validity, three review authors (MM, BN, EJO) piloted a predesigned form by extracting data from three (60%) of the included studies. We modified the form based on the pilot. Thereafter, one review author (MM or BN, or EJO) extracted data from the included studies using the finalized form and a second review author (MM) verified the information. We resolved disagreements through discussion and consensus-building. We extracted the following data: first author, date of publication, setting (country, type of health facility, country income level, and TB and HIV burden), study design, type of participant (patient or HCW), method of data collection, type of data analysis (such as thematic and framework), and reported experiences and perspectives. We assigned country income levels according to the World Bank List of Economies [14]. In addition, we classified countries as being a high burden or not a high burden for TB, HIV-associated TB, and multidrug-resistant (MDR)/rifampicin-resistant TB based on the WHO classification for the period 2021-2025 [15].

Assessment of methodological quality
We assessed the methodological quality of the studies using the Evidence for Policy and Practice Information (EPPI) Centre tool, which has been used in other qualitative reviews [16,17]. We assessed the following domains using the tool: rigour in the sampling, rigour in the data collected, the rigour of data analysis, support of the findings from the data, breadth and depth of the findings, reliability of the study findings, and relevance of the study findings to the aims of the synthesis. Based on predefined criteria provided by the EPPI Centre tool, domains were scored as yes, a fairly thorough attempt was made; yes, several steps were taken; yes, a few steps were taken; and no, not at all/can't tell. MM, with either EJO or BN, applied the EPPI Centre tool independently and we resolved any disagreements through discussion and consensus-building.

Data synthesis and analysis
We analysed the data separately for patients and HCWs as we expected to find differences between these two groups. We conducted the synthesis of data using five stages of the thematic framework synthesis as follows [18,19]. One review author (MM) familiarized herself with the data against the QES objective and noted recurrent themes across studies. We used a predetermined thematic framework developed by SURE guidelines to guide the thematic analysis [13]. We adopted the framework based on the emerging themes from the included studies. The framework provided a list of factors that contributed to PTLFU and possible strategies to reduce PTLFU. MM, with either BN or EJO, independently reviewed the data to identify themes. As new themes emerged, we modified the framework. We continued this process through discussion and consensus until there were no new emerging themes. We coded and sorted data based on the themes identified in the primary studies and displayed the themes in an analysis table (Chart). Specifically, we presented studies and related themes in columns and rows of the table, thereby enabling the review authors to compare the findings of the studies across different themes and subthemes. We explored associations between themes to help clarify our findings. We mapped and interpreted the findings by the QES objective and emerging themes.

Assessing our confidence in the QES findings
We used GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative Research) to assess confidence in the QES findings [20]. GRADE-CERQual includes four key components: methodological limitations of included studies; coherence of the QES findings; adequacy of the data contributing to the QES finding; and relevance of the included studies to the QES question. MM initially assessed the confidence in each QES finding and EO checked her assessment, resolving any disagreements by discussion. We classified overall confidence as high, moderate, low, or very low. We presented the CERQual assessment and explanations in a Summary of findings table.

Study selection
We identified a total of 1720 records through database searching. After removing the duplicates, we screened 1239 records by title and abstract to remove irrelevant reports and excluded 1111 records. We retrieved 128 reports and, after assessing them against the inclusion and exclusion criteria, excluded 123 reports (see Supplemental material 2). The main reason for exclusion was the ineligible concept (n = 71), which we described further as the loss to follow-up during treatment (n = 30); delayed diagnosis of TB (n = 21); TB programme related (n = 15); not pulmonary TB (i.e. latent TB infection, extrapulmonary TB) (n = 4); and delayed initiation of treatment (n = 1). We finally included a total of five studies in the QES [21][22][23][24][25] (Figure 1).

Characteristics of included studies
Of the five included studies, three studies used qualitative methods (critical incident narratives, exploratory and grounded theory) only [21,24,25], while two used a mixed methods approach [22,23]. Three studies were from India [22,23,25], one from Malawi [21], and one from South Africa [24]. The participants were HCWs, TB programme managers, patients who experienced PTLFU, and family members of the patients who experienced PTLFU and had died. The studies were in both rural and urban settings and included primary, secondary, and tertiary care facilities. Three studies took place in lower-middle-income settings [22,23,25], one study in an upper-middle-income setting [24], and one study in a low-income setting [21]. All studies were from high TB/HIV burden countries while four of the studies were from high TB and MDR-TB burden countries [22][23][24][25] Table 1.

Assessment of methodological quality
All studies had taken several steps in ensuring there was rigour in sampling in that there was variation in the participants who were interviewed. Three studies did not report detailed demographic characteristics for their participants [21][22][23]. Regarding rigour in data collection, four studies had taken several steps in ensuring data collection tools were well prepared, informed consent was conducted with the participants, and more than one method of data collection was used. Only one study reported piloting the data collection tool [24]. One study indicated there was written informed consent, but the process was not described [22]. One study reported on the duration of the interviews [25]. Rigour in data analysis was fairly well done in most of the studies with two of the studies making a thorough attempt [24,25]. These two studies described their data analysis methods in detail and had a second person review the data to ensure that the information provided by the participants was accurately captured. One study had insufficient participant quotes, and these were not coded to support the themes that arose during the brainstorming session and the focus group discussion [24]. Study findings were adequately supported by the data (participants' quotes) in three studies [21,24,25]. In terms of depth and breadth of study findings, in one study, the authors made a thorough attempt at exploring different reasons for PTLFU, going beyond the descriptive data provided by the participants to come up with an explanatory model [25]. One study had limitations when it came to breadth and depth in that the authors included few quotes to support the findings, and these were mainly from the patients who experienced PTLFU [23]. The study had  *The publication refers to initial loss to follow up though the definition is similar to PTLFU, that is why we included the paper.
only two quotes from the HCWs to support their perspectives, (Supplemental material 3). We have provided a detailed assessment in Supplemental material 4.

QES findings
We grouped the factors contributing to PTLFU into those related to patients, HCWs, and the healthcare system ( Figure 2).

QES themes
Themes related to patients are described in Table 2, HCWs in Table 3, and the healthcare system in Table 4.

Theme 1: patients' knowledge, attitudes, and behaviours about TB and its management
Overall, patients reported having limited knowledge about the cause of TB. Although some patients described TB as a gradual deterioration in health accompanied by a persistent cough, others thought the disease was caused by 'bad air' (Q1). Some patients were unaware that their symptoms could be related to TB while others associated a TB symptom such as cough with having HIV/AIDS. Moreso, people with TB who use alcohol and drugs reported they were concerned that, after starting TB treatment, they would be unable to continue to use these substances (Q6).

Theme 2: patients' motivation to attend TB appointments
Patients mentioned several reasons affecting their motivation to attend TB appointments leading to PTLFU: lack of support from family members (Q7), TB-related stigma (Q8, Q9), lack of housing (Q10), and inability to pay for medical expenses (Q11).
' . . . MK. 100.00 was not enough so we just decided to buy some medication so that it could help, and I think it took almost one week until she died.' (Father of the deceased, Malawi) [21].    Patients reported having unpleasant experiences when they visited the health facilities such as the treatment they received from the HCW (Q19) and being scolded by the HCW (Q20).

Theme 4: accessibility and availability of facilities for TB care
Patients reported that cost and time travelling due to the frequent visits (Q21) and long distance (Q22) to the TB centres dissuaded them from accessing care.
Additionally, patients were discouraged when they reached the health facility and did not receive care due to long waiting times (Q23, Q24), lack of pharmacy supplies (Q25), and failure of the power supply. After encountering these barriers, some patients never returned.
"Thrice I came to (a tertiary hospital) to receive my test report but . . . they said, ' . . . you have to wait for some days . . . We can prepare your report only when the power supply is available.' (Woman without a prior treatment history, India) [25].

Theme 5: human resource and financial constraints
HCWs reported having out-of-pocket expenses for which they were not reimbursed (Q26, Q27). These financial constraints limited them from performing their roles effectively. Examples are sending a referral form via courier to the TB care facility, making phone calls, and covering the travel costs required to follow up with patients.
'Due to practical difficulties, we never send this column (copy of the referral form). If I have to send this column (back to the Diagnostic Microscopy Centre (DMC)) then I need to spend money from my pocket for purchasing the envelope and paying the courier charge.' (Participant in a senior treatment supervisor FGD, India), [25].
Although some HCWs received a travel allowance, they were less inclined to provide follow-up visits with patients because they felt the allowance was inadequate.
'Inadequate motivation of staff for conducting default retrieval, long-distance between DOT centre and catchment area, lack of transport facility for health visitor to make retrieval visits. Conveyance allowance for the TB health visitor is considered inadequate by them resulting in decreased motivation of staff for conducting home visits.' (Brainstorming session of TB programme managers, India) [22].
Regarding human resources, HCWs pointed to the high workload as a factor contributing to PTLFU. Most mentioned that owing to staff shortages they had to work at more than one facility which caused delays between sputum collection and receipt of test results (Q28). Additionally, HCWs were not able to execute their duties as required such as verification of patient contact information, especially those working in high-volume facilities.
'It is very difficult (to verify patient contact information) in big centres (i.e. high-volume facilities) because they are regularly overcrowded with patients.' (Participant in a senior treatment supervisor FGD, India) [25].
Other reasons related to human resources that contributed to PTLFU comprised frequent staff rotation at the TB clinics that disrupted continuity of care (Q29) and lack of teamwork amongst the staff at the TB centres (Q30). This happened mostly when the staff at the TB clinic was on leave. 'There are some issues when TB health visitor (TBHV) is on leave. Other staffs are busy with their own works. They are not willing to take additional responsibilities of TBHV . . . .' (Senior treatment supervisor, India) [23].

Theme 6: challenges in internal and external communication in the TB healthcare facilities
Communication among HCWs and coordination in and between facilities were challenges that contributed to PTLFU. Patients experienced frustration during referrals from one facility to another (Q31).
'Doctors in medical college were not in favour of intermittent therapy, therefore after investigations at DMC, they started the patient on treatment but did not provide any feedback regarding treatment to the specific DOT/DMC where the sputum was tested.' (FGD of medics and paramedics, India) [22].
Similarly, communication between HCWs and patients was a contributor to PTLFU. After learning that their sputum tested positive for TB, patients were not clear about the next steps and what to do when they were referred from one facility to another (Q32). In addition, HCWs had poor communication and counselling skills (Q33, Q34). Consequently, patients were reluctant to return to the facility when the referral from one clinic to another was frustrating. 'We went to (a tertiary hospital) for an initial checkup . . . . They didn't tell us much. They said go to number 3 (outpatient clinic) and then number 5 (outpatient clinic) and back again for 2 days. After running from pillar to post, we just gave up and returned home.' (Family member of a man without a prior treatment history, India) [25].

Theme 7: education and training
Some HCWs had not been trained in TB management, which contributed to the interruption of TB services when trained TB staff were unavailable (Q35).
In some settings, most of the patients who experienced PTLFU had special needs such as migrants and people who use drugs and alcohol [22,23,25]. However, HCWs lacked the knowledge and skills to reach out to people with special needs.

Theme 8: management and leadership in the TB programme
Concerns were voiced regarding the management and leadership of the TB programme which led to PTLFU. Teamwork and capacity to make decisions on TB care were lacking among the HCWs, which consequently affected the delivery of TB health services (Q36, Q37). Additionally, junior staff felt overworked and disrespected when senior staff gave them assignments unrelated to TB care (Q38, Q39). Also, the working hours at the directly observed treatment (DOT) centres (also referred to as treatment support centres) were not people-centred, especially for those who were running businesses and women who had other responsibilities at home.
'At the grass-root level, the programme has its functional units as DMCs and DOT centres catering to specific areas. DOT centres located at public health facilities have fixed timings (8 am-2 pm) that may be inconvenient for different sections due to reasons related to working hours.' (Brainstorming session of TB programme managers, India) [22]. Also, the paperwork during patient referral was not clear, which led to patients dropping out of care when they were sent to the referring facility for more documents.
After the patient reached the rural DOT centre, the HCW said): 'Go back to (tertiary hospital where the patient was diagnosed in the city) and bring a referral slip -only then can we start treatment.' (Man without a prior treatment history, India) [25].

Confidence in the QES findings
We used GRADE-CERQual to assess our nine review findings. We graded three themes as high confidence and six themes as moderate confidence. The summary of findings is presented in Supplemental material 5. We have provided a detailed assessment including explanations for our grading (see Supplemental material 6).

Discussion
Our QES found that many factors contribute to PTLFU. Central to addressing these factors will be the need to strengthen health systems and offer people-centred care, which are vital to ensuring good patient outcomes. Reported healthcare systemrelated factors consist of accessibility and availability of facilities for TB care, human resource and financial constraints, communication among HCWs and between HCWs and patients, coordination in the different TB care facilities, training for HCWs, and management and leadership in the TB programme.
Reported patient-related factors comprise knowledge, attitudes, and behaviours about TB and its management and motivation towards keeping TB appointments or going to the clinic. Reported HCW-related factors include knowledge, attitudes, and behaviours about TB and its management. Using GRADE-CERQual, we had moderate confidence in most of our findings.
To our knowledge, this is the first QES on patients' and HCWs' perspectives on factors contributing to PTLFU. Strengths of the QES include searching multiple databases and having more than one reviewer involved at every stage of the synthesis including study selection, quality assessment, and data extraction. However, we did not search the grey literature and limited the studies to those published in English; thus, there is a possibility that we might have missed some relevant studies.
Our findings highlight some of the challenges that patients face when navigating the TB care cascade. Breakdown in communication between HCWs and patients concerning the next steps after diagnostic testing was cited as one of the obstacles to starting treatment [26,27]. This challenge needs to be addressed early in the TB care cascade otherwise it will also contribute to patients dropping out after they start treatment [28]. Other reported factors contributing to PTLFU are related directly to patients such as using alcohol and being an immigrant [27,29,30]. Stigma is still an impediment when it comes to patients starting treatment. This is similar to the findings from a QES on adherence to TB treatment [31]. Patients shy away from starting the medications since their relatives and people close to them will get to know their situation and view them as having human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Long waiting times and frequent visits to the TB clinic also discouraged patients. Patients who work had to choose between going to the clinic and losing a day's wages, and most opted to work in lieu of attending the clinic.
The lack of counselling about TB was reported as a factor affecting PTLFU. Counselling is important for TB care in that it enhances better patient outcomes by improving patients' knowledge about TB and dispelling misconceptions about the disease [32,33]. HCWs can then clearly explain the meaning of test results and provide support as patients try to cope with the stress of the diagnosis. This is an opportunity to establish trust, correct misperceptions about TB, and encourage patients to start treatment.
Regarding the health system, we noted several concerns that may have affected HCW attitudes and interactions with patients leading to PTLFU [24,25]. For instance, staff shortages in the TB programme led to more work for those who were available. These shortages contributed to delays in patients receiving their test results and some did not return to the facility. Moreover, when the workload was high, HCWs could not spend adequate time with patients. Thus, patients did not receive information about what to do after collecting their test results and counselling on the importance of starting treatment. In addition, HCWs reported that contact details were frequently not verified during registration.
Limited financial support was also a barrier to the provision of TB services. HCWs reported that they did not receive enough financial support when it came to patient follow-up. Money for transportation and phone calls was not forthcoming. This resulted in HCWs becoming discouraged and in turn, they did not track patients who missed their clinic visits. Some HCWs went the extra mile in using their own money and resources for patient follow-up, but they were not reimbursed. This led HCWs to discontinue following up with patients leading to PLTFU.
National TB programmes should use routinely available data to address PTLFU. For example, TB programmes can monitor the proportion of notified TB cases that have bacteriologically confirmed disease and ensure that these patients are followed. Ultimately, placing people at the centre of care will enable HCWs to provide care holistically, knowing that apart from having TB, patients may face other challenges, such as food insecurity and lack of housing. Food insecurity and lack of housing are among the factors which may increase the risk of TB infection, disease, and poor clinical outcomes [34,35]. In addition, the recently published WHO 'Guidance for national strategic planning for tuberculosis' will facilitate the creation of comprehensive plans for TB at national and subnational levels [36]. The WHO guidance emphasizes the importance of high-level political commitment to ensuring adequate resources for TB care and prevention [2,36].
Of the five included studies in this QES, three were from one country [22,23,25]. We note this as a limitation because the factors identified in these studies may not apply to all settings. Four studies used an exploratory design. More qualitative studies should be done in different settings and using other designs such as ethnography to find out if the reasons across different settings and countries are similar. This information will be useful in informing policy regarding addressing PTLFU globally and in different settings.

Review author reflexivity
The review author team has a range of research experience and expertise in clinical research and evidence synthesis in TB. This could have influenced their input in conducting the QES, therefore the following measures were factored in to moderate their influence. During the study selection process, the review authors resolved conflicts through discussion and aimed to achieve consensus as a team. Two review authors who were involved in data extraction and writing up the findings repeatedly discussed how their backgrounds may influence their data analysis and writing of the findings. They also questioned each other's interpretations of the findings to assess their fit with the existing findings. The other review authors were also consulted to verify that the findings were reflections of the supporting data.

Conclusion
In this QES, we found that multiple factors contributed to PTLFU, the main ones being the need to offer people-centred care and strengthen health systems. To be effective, interventions to address PTLFU should consider the concerns of patients and providers and place patients at the heart of care in the health system. Political commitment at the national level is needed to ensure adequate resources for addressing PTLFU and moving closer to the goal of ending TB.

Disclosure statement
No potential conflict of interest was reported by the author(s).

Funding information
This study is funded under the UK MRC African Research Leaders award (MR/T008768/1). This award is jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO) under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 programme supported by the European Union." This publication is associated with the Research, Evidence and Development Initiative (READ-It) project. READ-It (project number 300342-104) is funded by UK aid from the UK government; however, the views expressed do not necessarily reflect the UK government's official policies."

Contributions of authors
MM, EO, KRS, and TY contributed to the QES protocol. MM, BN, EJO, and KRS screened the studies. MM developed the data extraction tool, and all authors gave their input before the data extraction process started. MM, BN and EJO conducted data extraction. All authors gave their input on the description, appraisal, and synthesis of data. MM wrote the first draft of the manuscript and all authors contributed to the writing of the manuscript.

Ethics and consent
For this QES, a formal ethical review was not pursued since the data collected was retrospective and available to the public.

Paper context
In the tuberculosis care cascade (model used to describe healthcare delivery), pre-treatment loss to follow-up has been shown to contribute substantially to patient losses, with subsequent high community transmission and mortality. Our qualitative evidence synthesis provides comprehensive evidence on contributors to pre-treatment loss to follow-up in adults with pulmonary TB and highlights areas to intervene. To achieve optimal care, it is vital to strengthen the healthcare system and offer people-centred care.